We are studying the response of the arterial wall to endothelial injury, in terms of endothelial regeneration and myointimal proliferation. To these ends the air-drying rat carotid injury model, and perfusion of an isolated segment of the carotid will be utilized in vivo, and tissue culture of endothelial and smooth muscle cells in vitro. The following will be studied: the effects of modulation by chemical means of subendothelial substrata on endothelial regeneration; the possible inhibitory effects of heparin fractions and other polyanions on myointimal proliferation, and the mechanism of action; the factors controlling the formation of luminal smooth muscle cells, and their surface properties as compared with endothelium; possible growth regulatory interactions between endothelium and smooth muscle, and the effects, and mechanisms of action, of various forms of stress in producing endothelial injury.